Eocene Lake Gosiute in southwestern Wyoming was progressively filled in by volcaniclastic sediment between 49.6 and 47.0 Ma. The source of this material has long been thought to have been the Absaroka volcanic province, immediately north of the greater Green River Basin. Lead isotope compositions of sandstone from this interval, however, are consistent with derivation from the Challis volcanic field. The 40Ar/39Ar ages of single detrital K-feldspar crystals from greater Green River Basin sandstones are nearly identical to 40Ar/39Ar eruptive ages for volcanic rocks of the Challis volcanic field (49.8–45.5 Ma), but we also identify Mesozoic and Proterozoic crystals that are consistent with cooling ages for rocks that were likely exposed in the Idaho segment of the North American Cordillera during the Eocene. Most of these rocks are traversed by or are up-gradient of a major Eocene paleovalley in central Idaho. The sudden appearance of Challis-derived sediment in the greater Green River Basin indicates that a major river, here named the Idaho River, connected the interior of the North American Cordillera to the greater Green River Basin. This connection requires 500 km to reach from central Idaho to the greater Green River Basin. The Idaho River probably carried detritus that was stripped from distant uplifted mountains above the active Challis volcanic field as far south as the Piceance Creek Basin, suggesting a total length of at least 1000 km. Middle Eocene metamorphic core complexes in the northern Cordillera likely produced a major highland in the headwaters of the Idaho River, which generated river systems that drained both eastward into the Wyoming foreland and westward into the Oregon Coast ranges.